CA2+ RELEASE AND CA2+ ENTRY INDUCED BY RAPID CYTOSOLIC ALKALINIZATION IN JURKAT T-LYMPHOCYTES

被引:33
作者
GUSE, AH [1 ]
ROTH, E [1 ]
EMMRICH, F [1 ]
机构
[1] UNIV ERLANGEN NURNBERG,INST CLIN IMMUNOL,MAX PLANCK SOC,CLIN RES UNIT RHEUMATOL IMMUNOL,D-91054 ERLANGEN,GERMANY
关键词
D O I
10.1042/bj3010083
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
4-Aminopyridine (4-AP), a compound usually known as a K+-channel inhibitor, induced rapid cytosolic alkalinization from pH 7.15 to pH 7.4, and subsequently Ca2+ mobilization in the T-lymphocyte cell line Jurkat. Other weak bases, such as NH4Cl or triethanolamine, induced a smaller and/or slower increase in cytosolic pH, resulting in a lower or no detectable Ca2+ signal. In the presence of extracellular Ca2+, 4-AP mediated a rapid and sustained increase in the free cytosolic Ca2+ concentration similar to that obtained by T-cell receptor-mediated stimulation. In the absence of extracellular Ca2+, 4-AP transiently released Ca2+ from an intracellular store that is most likely identical with the agonist- and Ins(1,4,5)P-3-sensitive Ca2+ pool of Jurkat T-cells. As possible mechanisms for Ca2+ release from this particular pool as induced by 4-AP we examined (i) formation of Ins(1,4,5)P-3 and (ii) sensitization of the Ins(1,4,5) P-3-receptor/Ca2+-release system by increasing intracellular pH. Although 4-AP did not induce formation of inositol polyphosphates, as demonstrated by h.p.l.c. analysis, in permeabilized cells the dose-response curve for Ins(1,4,5)P-3 was shifted to the left by changing the intracellular pH from 7.2 to 7.4. This indicated that sensitization of the Ins(1,4,5)P-3-receptor/Ca2+-release system was responsible for the effects of 4-AP seen in intact cells. In conclusion, 4-AP appears a novel tool for depletion of the agonist-sensitive Ca2+ pool of T-cells without simultaneous formation of Ins(1,4,5)P-3, thereby inducing capacitative Ca2+ entry in these cells.
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页码:83 / 88
页数:6
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